Historically, infectious agents such as bacteria, fungi, parasites, and viroids have well established methods of control that involve various forms of disinfection and sterilization (e.g. steam sterilization, dry sterilization, pasteurization, sterile filtration, treatment with ethylene oxide, glutaraldehyde, phenols or other disinfecting chemicals, radiation, etc.). With viruses, there are also established methods for example lowering the pH to 4.0 or below, heating at 60° C. for extended periods, or use of organic solvents in high concentrations. In addition, UV treatment, formaldehyde and specific antiviral agents have been employed.
For some years now, new and previously unknown species of pathogenic agents have appeared and have been reported in scientific publications. These have been referred to as prions and present one of the greatest challenges facing the health care industry today. Prions are infectious particles that differ from bacteria and other previously known infectious agents. While there is no firm evidence on the exact structure of prions, a number of diseases have been identified recently both in humans and animals, that appear to be attributable to prions. As detailed in PCT/US00/14353 (the content of which is incorporated herein by reference), human diseases attributed to prions include Kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease (GSS), and Fatal Familial Insomnia. (FFI).
In addition to prion diseases of humans, disorders of animals are included in the group of known prion diseases. Scrapie of sheep and goats is perhaps the most studied animal prion disease. Several lines of inquiry have suggested a link between variant CJD and a preceding epidemic of bovine spongiform encephalopathy (BSE). No successful therapeutic treatments have been developed and as a result these diseases are always fatal. Adding to the problem is the fact that the incubation period can be up to 30 years in humans and this factor presents a major challenge to the scientists involved, with some predicting an epidemic “in the pipeline”.
Groups possibly at risk of infection include patients who may come into contact with infected medical instruments during surgery, medical staff dissecting infected material, and healthcare workers responsible for cleaning and sterilizing instruments. There are also concerns that groups at risk may be broadened to include veterinarians, abattoir workers, butchers in contact with cows or beef primarily in Europe and more recently persons receiving blood transfusions or organs from donors incubating a prion disease.
The structure of prions has been the subject of intense investigation and different points of view have been expressed. Some scientists believe they are extremely small viruses, while most experts now believe that prions are actually infectious proteins without a DNA or RNA core. More particularly the consensus now is that the PrP gene of mammals expresses a protein which can be the soluble, non-disease, cellular form PrPc or can be an insoluble disease form PrPsc. Many lines of evidence indicate that prion diseases result from the transformation of the normal cellular form into the abnormal PrPSc form. There is no detectable difference in the amino acid sequence of the two forms. The PrPc form is composed of a highly membrane associated 33-35 kDa protein which degrades on digestion with protease K. However the PrPSc form has an altered conformational form, in particular having a high level of β-sheet conformation. Properties of PrPSc useful in diagnosing the infective altered conformational form are a protease resistant core of 27-30 kDa. Another distinctive feature of the altered conformational infective form is that it acquires a hydrophobic core.
Conventional disinfection and sterilizing agents have no significant effect on prions in an acceptable time. Attempts to deactivate prions and/or to disinfect surfaces on which they may be transmitted have shown an extraordinary resistance. The conditions required are generally too severe to be practical for routine disinfection, not only in terms of time and cost, but also in terms of damage to materials and occupational health hazards involved. For example in one study infectious PrPSc particles have been detected in a sample after 5-15 mins/600° C. dry heat although total destruction could be achieved at 1000° C. in 15 mins and in from 1-10 hrs at >200° C. It has been proposed to treat with I M. caustic soda (pH14) for 2 hrs but that treatment is extremely corrosive, dangerous to staff, and aggressive to materials. U.S. Pat. No. 5,633,349 describes a procedure for treating a biological material involving treatment with 6-8 molar urea or 1-2 molar sodium thiocyanate for a minimum of 12 hrs (preferably 18 hrs) which suffers from similar disadvantages.
Because of the difficulties in decontamination it has been proposed as preferably that surgical instruments used in brain surgery should be used only once, but this implies a disposal risk in addition to being expensive and for some instruments impractical. PCT/US00/14353 describes a method of rendering prions non-infectious by use of a polycationic dendrimer but it is not clear whether that process is reversible or permanent or commercially viable for disinfecting surfaces.
Although attention has been focused on the PrPc form and the PrPSc form it has also been suggested that the protein can exist in an intermediate form which has a β-sheet content intermediate between the predominantly alpha helix structure of the PrPc form and the predominantly β-sheet conformation of the PrPSc form and which retains solubility in the absence of a denaturant.
The assembly or misassembly of normally soluble proteins into conformationally altered insoluble proteins is thought to be causative of, or implicated in, a variety of other diseases. Although the invention will be herein described in relation to prions, it will be understood to be applicable to other insoluble or enzyme resistant conformationally altered proteins implicated in disease.
The above discussion of prior art is not to be construed as an admission with regard to the common general knowledge in Australia.